A. Neuroviraology. The pathogenesis of human immunodeficiency virus (HIV)-induced encephaopathy is being studies by using two approaches. Firstly, by understanding the interaction of HIV-1 isolates, in general, with the neural tissues. Secondly, by detailed biological and molecular characterization of HIV-1 variants isolated from persons with neurological deficiencies, especially in the absence of overt immune suppression. The second approach is expected to elucidate if certain strains of HIV-1 are uniquely neuropathic. The virus-cell interaction studies have shown that human neural cell lines can be transfected with HIV DNA resulting in transient virus replication. Currently, our preliminary findings using primary rodent brain cultures reveal that HIV can partially replicate in these cells upon direct infection, and is specifically cytopathic to neural cells. We have biologically and molecularly characterized one of HIV-1 isolates (HIV-br) and have observed the presence of a 39-base duplication of nucleotides in the nef gene. B. Antiviral Agents. We have investigated the anti-HIV activity of sodium pentosan polysulfate (PPS), a sulfated sugar compound, normal human peripheral mononuclear cells (PMNC). PPS has potent anti-HIV activity, shows profound anti-HIV synergism with AZT, is essentially nontoxic to PMNC and has lymphoproliferative effect in culture.